Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients.

OBJECTIVES: We have previously shown that treatment with intranasal sodium citrate may be beneficial in post-infectious olfactory dysfunction. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. We also aimed to determine whether sodium citrate is beneficial in treating qualitative olfactory dysfunction. METHODS: We performed a prospective, controlled study. Patients applied intranasal sodium citrate solution to the right nasal cavity for 2 weeks. The left nasal cavity was untreated and, therefore, acted as an internal control. Monorhinal olfactory function was assessed using the "Sniffin' Sticks" composite 'TDI' score, before and after treatment. The presence of parosmia and phantosmia was also assessed. RESULTS: Overall, there was a significant increase in TDI after treatment (using the best of right and left sides). Treatment with sodium citrate did not significantly improve quantitative olfactory function, compared to control. The proportion of patients reporting parosmia did not change significantly after treatment. However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period. CONCLUSIONS: Treatment with intranasal sodium citrate for a period of 2 weeks does not appear to improve quantitative olfactory function in patients with post-infectious impairment, compared to control. It may, however, be beneficial in treating phantosmia, which should be further addressed in future work.

Comparison of COVID-19 and common cold chemosensory dysfunction.

Anosmia constitutes a prominent symptom of COVID-19. However, anosmia is also a common symptom of acute colds of various origins. In contrast to an acute cold, it appears from several questionnaire-based studies that in the context of COVID-19 infection, anosmia is the main rhinological symptom and is usually not associated with other rhinological symptoms such as rhinorrhoea or nasal obstruction. Until now, no study has directly compared smell and taste function between COVID-19 patients and patients with other causes of upper respiratory tract infection (URTI) using valid and reliable psychophysical tests. In this study, we aimed to objectively assess and compare olfactory and gustatory functions in 10 COVID-19 patients (PCR diagnosed, assessed on average 2 weeks after infection), 10 acute cold (AC) patients (assessed before the COVID-19 outbreak) and 10 healthy controls, matched for age and sex. Smell performance was assessed using the extended "Sniffin' Sticks" test battery (4), while taste function was assessed using "taste strips" (5). Receiver Operating Characteristic (ROC) curves were built to probe olfactory and gustatory scores in terms of their discrimination between COVID-19 and AC patients. Our results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients. In the future, studies to assess the prevalence of persistent anosmia and neuroanatomical changes on MRI correlated to chemosensory function, will be useful to understand these mechanisms.

Structural Plasticity of the Primary and Secondary Olfactory cortices: Increased Gray Matter Volume Following Surgical Treatment for Chronic Rhinosinusitis.

Functional plasticity of the adult brain is well established. Recently, the structural counterpart to such plasticity has been suggested by neuroimaging studies showing experience-dependent differences in gray matter (GM) volumes. Within the primary and secondary olfactory cortices, reduced GM volumes have been demonstrated in patients with olfactory loss. However, these cross-sectional studies do not provide causal evidence for GM volume change, and thereby structural plasticity. Disorders of the peripheral olfactory system, such as chronic rhinosinusitis (CRS), provide an ideal model to study GM structural plasticity, given that patients may experience long periods of olfactory impairment, followed by near complete recovery with treatment. We therefore performed a prospective longitudinal study in patients undergoing surgical treatment for CRS. We used voxel-based morphometry (VBM) to investigate GM volume change in 12 patients (M:F = 7:5; 47.2 ±â€¯14.9 years), 3 months post-op. There was a significant improvement in olfactory function according to birhinal psychophysical testing. We performed a voxel-wise region of interest analysis, with significance corrected for number of regions (p < 0.0036corr). We found significantly increased post-operative GM volumes within the primary (left piriform cortex, right amygdala) and secondary (right orbitofrontal cortex, caudate nucleus, hippocampal-parahippocampal complex and bilateral temporal poles) olfactory networks, and decreased GM volumes within the secondary network only (left caudate nucleus and temporal pole, bilateral hippocampal-parahippocampal complex). As a control measure, we assessed GM change within V1, S1 and A1, where there were no suprathreshold voxels. To our knowledge, this is the first study to demonstrate GM structural plasticity within the primary and secondary olfactory cortices, following restoration of olfaction.

Mutation in Nav 1.7 causes high olfactory sensitivity.

Mutations in the sodium-channel Nav 1.7, encoded by the gene SCN9A, are known to cause pain disorders. In particular, gain-of-function missense mutations in Nav 1.7 have been shown to be causal in primary erythromelalgia. We present a patient with erythromelalgia, pain attacks and hyperosmia with a mutation within the sodium-channel gene SCN9A. A 50-year-old woman presented with burning pain in both feet and abdominal pain attacks developed over the course of 10 years. Furthermore, this patient experienced a hypersensitivity for odours. Clinical investigation as well as serum/cerebrospinal fluid laboratory findings and electrophysiological testing were unremarkable. Olfactory testing showed high olfactory acuity for all screened modalities and good intranasal sensitivity. Furthermore, quantitative sensory testing within the trigeminal area revealed very low thresholds for thermal, tactile and pain detection. In addition, quantitative sensory testing at the lower legs showed hyperalgesia and, as the disease progresses, thermal sensory function loss. Skin biopsies of the proximal and distal lower limbs revealed reduced epidermal nerve fibre density indicating small fibre neuropathy. Genetic analysis of the SCN9A gene demonstrated a heterozygous mutation in Exon 20 - c.3734A>G (p.N1245S). Treatment with clinically available sodium-channel inhibitors did not result in significant pain relief. Local application of the sodium-channel blocker ambroxol however, reduced pain intensity. Continuous odour exposure stabilised mood and induced a short-term pain relief. This clinical note illustrates the course of middle-age onset erythromelalgia and points to clinical findings related to a likely pathogenic missense mutation affecting the sodium-channel Nav 1.7. SIGNIFICANCE: This case report illustrates the course of middle-age onset erythromelalgia with presumed gain-of-function in olfactory and pain sensation associated with a Nav1.7 channel mutation.

The confounding effect of background odors on olfactory sensitivity testing.

BACKGROUND: Human olfactory sensitivity is known to vary significantly across subjects. Furthermore, environmental factors such as background noise and odor are known to affect target odor threshold scores but have not yet been fully delineated. We aimed to determine whether congruent and non-congruent background odor impaired target odor threshold scores. NEW METHOD: We performed odor threshold testing in 103 normosmic adults, using phenylethylalcohol (PEA) or linalool as target odors, under three conditions: (a) congruent target and background odors (e.g., PEA in the test and PEA in the background), (b) non-congruent target and background odors (e.g. PEA in the test and Linalool in the background) and (c) no background odor. Background odor was applied to the investigator's glove and testing was performed in an otherwise odorless room. RESULTS: We found that congruent background odors significantly impaired target odor threshold scores. Non-congruent background odors also impaired target odor threshold, but significantly more so with PEA as target and Linalool as background odor. The best threshold scores were obtained with no background odor. Comparison with Existing Method(s). At present, many testing environments may be contaminated with ambient background odors. We have shown that this may negatively affect odor threshold scores, particularly where background and target odors are congruent. CONCLUSIONS: We suggest that investigators performing odor threshold testing do so in well ventilated, odor free environments.

Patient experience of nasal obstruction and its clinical assessment.

BACKGROUND: The correlation between objective and subjective nasal obstruction is poor, and dissatisfaction rates after surgery for nasal obstruction are high. Accordingly, novel assessment techniques may be required. This survey aimed to determine patient experience and preferences for the measurement of nasal obstruction. METHOD: Prospective survey of rhinology patients. RESULTS: Of 72 questionnaires distributed, 60 were completed (response rate of 83 per cent). Obstruction duration (more than one year) (χ2 = 13.5, p = 0.00024), but not obstruction severity, affected willingness to spend more time being assessed. Questionnaires (48 per cent) and nasal inspiratory peak flow measurement (53 per cent) are the most commonly used assessment techniques. Forty-nine per cent of participants found their assessment unhelpful in understanding their obstruction. Eighty-two per cent agreed or strongly agreed that a visual and numerical aid would help them understand their blockage. CONCLUSION: Many patients are dissatisfied with current assessment techniques; a novel device with visual or numerical results may help. Obstruction duration determines willingness to undergo longer assessment.

Short inter-stimulus intervals can be used for olfactory electroencephalography in patients of varying olfactory function.

Use of chemosensory event-related potentials (ERPs) is limited by relatively poor signal-to-noise ratios (SNRs). We hypothesized that by reducing the standard inter-stimulus interval (ISI), the increased number of trial repetitions possible may increase SNR. In order to further investigate this, we performed the largest study to date assessing chemosensory ERP using short and long ISIs in 101 participants of varying olfactory function. Using rose odor (phenylethylalcohol, PEA) as a relatively selective olfactory stimulant, we found no significant difference in the proportion of individuals in whom ERPs were recorded using short or long ISIs. This was true in normosmic, hyposmic and functionally anosmic individuals. We also demonstrated significantly increased SNR using short PEA-ISIs, in the normosmic and functionally anosmic groups. Comparing between groups of different olfactory function, hyposmic patients achieved faster onsets and greater amplitudes than normosmics under the PEA-10s protocol. This could be due to increased stimulus attendance, but requires confirmation with further research.

Peak nasal inspiratory flow correlates with quality of life in functional endoscopic sinus surgery.

OBJECTIVES: Whilst nasal function and airflow improve subjectively following functional endoscopic sinus surgery (FESS), a clinically useful and objective tool for quantifying such improvement is lacking. The peak nasal inspiratory flow (PNIF) metre offers convenient and objective measures of nasal patency. However, it has not yet been established whether changes in PNIF after surgery reflect changes in subjective disease burden. In this study we aimed to determine whether changes in PNIF correlate with commonly used subjective symptom and quality of life outcome measures following FESS for chronic rhinosinusitis (CRS). DESIGN: Prospective cohort. SETTING: Royal National Throat Nose and Ear Hospital. PARTICIPANTS: Thirty-seven patients undergoing FESS for CRS, with or without polyps (21 male, mean age 48.8). MAIN OUTCOME MEASURES: PNIF, "SNOT-22", "NOSE" and "VAS" questionnaires were performed before and after surgery. RESULTS: In all patients, there was a strong negative correlation between change in PNIF and change in "SNOT-22" score following surgery (Pearson r=-.64, P<.0001). Strong negative correlations were also seen during subgroup analysis of patients with and without polyps (r=-.57, P=.006 and r=-.67, P=.005, respectively). Change in PNIF correlated significantly with change in "NOSE" score following surgery in all patients and those without polyps (r=-.54, P=.0005 and r=-.68, P=.003). There were no significant correlations between PNIF and VAS (nasal obstruction). CONCLUSIONS: Changes in PNIF after FESS appear to best reflect improvements in quality of life in CRS as measured using the "SNOT-22" questionnaire.

Position paper on olfactory dysfunction.

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients.

OBJECTIVES: Free calcium plays an integral role in peripheral olfactory processing, including feedback inhibition. It has therefore been suggested that reduction of intranasal free calcium with buffer solutions such as sodium citrate may improve olfactory function in patients with smell impairment. Several previous studies have supported this hypothesis, particularly in post-infectious olfactory loss. We therefore aimed to determine whether treatment with intranasal sodium citrate improves olfactory function in patients with post-infectious impairment. DESIGN: Prospective, single-blind, placebo-controlled trial. SETTING: Interdisciplinary Smell and Taste Clinic, TU Dresden (tertiary referral centre). PARTICIPANTS: Forty-nine adult participants with post-infectious olfactory impairment (M : F = 11 : 38, mean age 58.71 ± 11.03 years). MAIN OUTCOME MEASURES: Olfactory function (odour threshold and identification) before and after treatment as determined using "Sniffin' Sticks". Patients were treated monorhinally with 1 mL sodium citrate solution. The contralateral nasal cavity was treated with 1 mL physiological sodium chloride solution, which acted as internal control. Clinical improvement was assumed where threshold or identification score increased by ≥2.5 or 3 points, respectively, or ≥5.5 points together. RESULTS: We demonstrated a statistically significant improvement in composite threshold + identification scores following treatment with sodium citrate, compared with placebo. This was true for all patients (mean improvement 0.87 ± 2.68 points, P = 0.04), and on subgroup analysis in those with hyposmia (mean improvement 1.15 ± 2.37 points, P = 0.02). However, the effect size did not reach clinical significance. CONCLUSIONS: Further basic and clinical work is required to fully delineate the effect of intranasal sodium citrate in the treatment of post-infectious olfactory loss.

Intranasal sodium citrate solution improves olfaction in post-viral hyposmia.

BACKGROUND: Calcium plays an integral role in olfactory signal transduction, including feedback inhibition. Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. We aimed to investigate the utility of intranasal sodium citrate in improving the olfactory function of hyposmic patients, by performing this prospective placebo controlled, single-blind trial. METHODOLOGY: Monorhinal olfactory testing for odour identification and threshold was performed in hyposmic patients using Sniffin Sticks, before and after treatment. Treatment consisted of one-off sodium citrate solution application to the olfactory cleft. Sodium chloride solution was applied to the contralateral olfactory cleft, which therefore acted as placebo control. Patients were blinded to the side of sodium citrate application, and side of treatment was randomized between patients. RESULTS: 57 patients participated, aged 22-79. Causes of hyposmia included: post-viral (7); posttraumatic (10); sinonasal disease (30) and idiopathic (10). Compared with placebo, there was significant improvement in the identification scores of participants with post-viral hyposmia, following sodium citrate treatment. No significant change in olfactory function occurred for either identification or threshold in any other aetiological subgroup. CONCLUSIONS: Intranasal sodium citrate may be of benefit to patients with post-viral hyposmia.

ENT and airways in the emergency department: national survey of junior doctors' knowledge and skills.

BACKGROUND: Given the urgent nature of ENT emergencies, appropriate knowledge is required amongst front-line staff. Junior doctors account for almost one quarter of emergency department doctors. It has been shown that undergraduate coverage of ENT is variable. This study therefore aimed to determine whether emergency department junior doctors were confident in dealing with ENT emergencies, with special focus on the airway. METHOD: An online survey was circulated to junior doctors working in emergency medicine, at the discretion of their training co-ordinators. RESULTS: A total of 104 responses were received. Junior doctors were not confident in managing patients who have undergone tracheostomy or laryngectomy. Management of stridor varied, with 51 per cent giving oxygen and only 77 per cent referring such patients as an emergency to ENT. Most training on the management of airway emergencies was not provided through hospital induction. CONCLUSION: Training should be provided to junior doctors starting work in the emergency department. We suggest mandatory multidisciplinary induction training for such staff.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.